Featured Research

from universities, journals, and other organizations

Protein may be key to new treatment in a childhood cancer

Date:

February 7, 2011

Source:

Children's Hospital of Philadelphia

Summary:

After analyzing hundreds of proteins produced by the DNA of tumor cells, researchers have identified one protein that may be central to a new treatment for the often-fatal childhood cancer neuroblastoma. Oncologists hope to translate the finding into pediatric clinical trials of a drug that blocks the protein's activity.

Share This

After analyzing hundreds of proteins produced by the DNA of tumor cells, researchers have identified one protein that may be central to a new treatment for the often-fatal childhood cancer neuroblastoma. Oncologists hope to translate the finding into pediatric clinical trials of a drug that blocks the protein's activity.

Related Articles

"Our study implicates this protein as a promising treatment target for high-risk neuroblastoma," said pediatric oncologist Kristina A. Cole, M.D., Ph.D., of the Cancer Center at The Children's Hospital of Philadelphia. "The fact that drugs acting on this protein are already being studied in clinical trials for adult cancers may hasten the process of testing this treatment strategy in children."

Cole is the lead author of a study published online Feb. 2 in the Proceedings of the National Academy of Sciences.

Neuroblastoma, a cancer of the peripheral nervous system, usually appears as a solid tumor in the chest or abdomen. It accounts for 7 percent of all childhood cancers, but because it is often aggressive, it causes 15 percent of all childhood cancer deaths. While low-risk forms of neuroblastoma may spontaneously disappear, in high-risk forms, the cancer tends to return after initial treatment, usually with lethal results.

In the current study, the Children's Hospital researchers performed a comprehensive screen of hundreds of protein kinases encoded by the DNA of neuroblastoma cells. As enzymes, kinases stimulate chemical reactions in the cell, and have been implicated in many cancers as promoting growth and survival of cancer cells. The study team used RNA interference, a powerful research tool that uses small RNA sequences to prevent cells from producing proteins, to interrupt the action of each of the more than 500 kinases made by neuroblastoma tumor cells.

Methodically testing each kinase, one after the other, the researchers identified 30 kinases that, when depleted, caused neuroblastoma cells to die. Among those kinases, cell checkpoint kinase 1 (CHK1) had the strongest effect. "This screen was an unbiased study," said Cole. "We did not know beforehand which kinase would have the most potent effect. In fact, we would not have suspected CHK1, which was thought to be a tumor suppressor. It actually has the opposite effect in neuroblastoma. Its signals appear to drive neuroblastoma growth, likely by allowing them to tolerate stress to DNA caused by the MYC and MCYN oncogenes, which are active in neuroblastoma. Blocking CHK1 activity by RNA interference or by small-molecule inhibitors kills neuroblastoma cells."

When cancer cells are treated with chemotherapy, they can repair themselves though CHK1 signaling, making the chemotherapy less effective. Normal cells have redundant repair pathways and are not affected by CHK1 inhibition. Therefore CHK1 inhibitors are already being tested in adult clinical trials, in combination with chemotherapy, as a possible treatment for lung cancer, pancreatic cancer and other solid tumors. The current study suggests that neuroblastoma cells are particularly sensitive to CHK1 inhibition, without being combined with other agents.

CHK1 is not the first kinase with an important role in neuroblastoma. Some of the collaborators in this study from The Children's Hospital of Philadelphia previously discovered that the anaplastic lymphoma kinase gene (ALK), which carries the code for the ALK kinase, gives rise to some high-risk forms of neuroblastoma. Children's Hospital is currently testing ALK inhibitors in pediatric clinical trials of neuroblastoma, under the sponsorship of the Children's Oncology Group, a cooperative multicenter research organization.

"While it is compelling that there is single-agent activity in neuroblastoma," said Cole. "we anticipate that CHK1 inhibitors combined with chemotherapy will be significantly more potent." Cole expects pediatric oncologists to begin testing CHK1 inhibitors in pediatric clinical trials for neuroblastoma within the next few years.

The National Institutes of Health, the Super-Jake Foundation, the Children's Neuroblastoma Cancer Foundation, the Alex's Lemonade Stand Foundation and the Abramson Family Cancer Research Institute provided financial support for this study. The corresponding author was John M. Maris, M.D., director of the Center for Childhood Cancer Research. All the co-authors are from both Children's Hospital and the University of Pennsylvania School of Medicine.

Children's Hospital of Philadelphia. "Protein may be key to new treatment in a childhood cancer." ScienceDaily. ScienceDaily, 7 February 2011. <www.sciencedaily.com/releases/2011/02/110207122015.htm>.

Children's Hospital of Philadelphia. (2011, February 7). Protein may be key to new treatment in a childhood cancer. ScienceDaily. Retrieved March 3, 2015 from www.sciencedaily.com/releases/2011/02/110207122015.htm

Children's Hospital of Philadelphia. "Protein may be key to new treatment in a childhood cancer." ScienceDaily. www.sciencedaily.com/releases/2011/02/110207122015.htm (accessed March 3, 2015).

More From ScienceDaily

More Health & Medicine News

Featured Research

Mar. 3, 2015 — Scientists have discovered a new hormone that fights the weight gain caused by a high-fat Western diet and normalizes the metabolism -- effects commonly associated with exercising. When tested in ... full story

Mar. 3, 2015 — New assays can detect malaria parasites in human blood at very low levels and might be helpful in the campaign to eradicate malaria, reports a new study. An international team led by Ingrid Felger, ... full story

Mar. 3, 2015 — Adults over the age of 30 only catch flu about twice a decade, a new study suggests. So, while it may feel like more, flu-like illness can be caused by many pathogens, making it difficult to assess ... full story

Mar. 3, 2015 — No significant change in home habits of smokers have been observed in the aftermath of a ban on smoking in public spaces, researchers report. Greater inspiration to kick the habit likely comes from ... full story

Mar. 3, 2015 — Heart function has been associated with the development of dementia and Alzheimer's disease through a new study. Participants with decreased heart function, measured by cardiac index, were two to ... full story

Mar. 3, 2015 — Children of recently separated or divorced families are likelier to drink sugar-sweetened beverages than children in families where the parents are married, putting them at higher risk for obesity ... full story

Mar. 3, 2015 — Gastric bypass and similar stomach-shrinking surgeries are a popular option for obese patients looking to lose weight or treat type 2 diabetes. While the surgeries have been linked to a decreased ... full story

Mar. 3, 2015 — Most people consume more salt than they need and therefore have a higher risk of heart disease and stroke, which are the two leading causes of death worldwide. But a new study reveals that dietary ... full story

Featured Videos

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015) — After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3)
Video provided by AP

Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

AFP (Mar. 3, 2015) — Thick black puddles and a looted, leaking ruin are all that remain of the Thar Jath oil treatment facility, once a crucial part of South Sudan&apos;s mainstay industry. Duration: 01:13
Video provided by AFP

Woman Convicted of Poisoning Son

AP (Mar. 3, 2015) — A woman who blogged for years about her son&apos;s constant health woes was convicted Monday of poisoning him to death by force-feeding heavy concentrations of sodium through his stomach tube. (March 3)
Video provided by AP

Related Stories

Nov. 10, 2014 — Oncology researchers studying gene mutations in the childhood cancer neuroblastoma are refining their diagnostic tools to predict which patients are more likely to respond to drugs called ALK ... full story

Apr. 16, 2014 — PCNA is a protein essential to DNA repair and replication, and researchers are targeting it in neuroblastoma cells in order to halt tumor growth and induce cell death. Neuroblastoma is one of the ... full story

May 23, 2013 — Nearly two-thirds of patients with high-risk neuroblastoma -- a common tumor that forms in the nerve cells of children -- cannot be cured using tumor-killing cancer drugs. A new study reveals a new ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.